Evidence-based standardized nutrition protocol can shorten the time to full enteral feeding in very preterm/very low birth weight infants / 中国当代儿科杂志

OBJECTIVES@#To investigate whether evidence-based standardized nutrition protocol can facilitate the establishment of full enteral nutrition and its effect on short-term clinical outcomes in very preterm/very low birth weight infants.@*METHODS@#A retrospective analysis was performed on the medical data of 312 preterm infants with a gestational age of ≤32 weeks or a birth weight of <1 500 g. The standardized nutrition protocol for preterm infants was implemented in May 2020; 160 infants who were treated from May 1, 2019 to April 30, 2020 were enrolled as the control group, and 152 infants who were treated from June 1, 2020 to May 31, 2021 were enrolled as the test group. The two groups were compared in terms of the time to full enteral feeding, the time to the start of enteral feeding, duration of parenteral nutrition, the time to recovery to birth weight, the duration of central venous catheterization, and the incidence rates of common complications in preterm infants.@*RESULTS@#Compared with the control group, the test group had significantly shorter time to full enteral feeding, time to the start of enteral feeding, duration of parenteral nutrition, and duration of central venous catheterization and a significantly lower incidence rate of catheter-related bloodstream infection (P<0.05). There were no significant differences between the two groups in the mortality rate and the incidence rate of common complications in preterm infants including grade II-III necrotizing enterocolitis (P>0.05).@*CONCLUSIONS@#Implementation of the standardized nutrition protocol can facilitate the establishment of full enteral feeding, shorten the duration of parenteral nutrition, and reduce catheter-related bloodstream infection in very preterm/very low birth weight infants, without increasing the risk of necrotizing enterocolitis.

Effect of prophylactic use of hydrolyzed protein formula on gastrointestinal diseases and physical growth in preterm infants: a Meta analysis / 中国当代儿科杂志

OBJECTIVES@#To systematically evaluate the effect of prophylactic use of hydrolyzed protein formula on gastrointestinal diseases and physical development in preterm infants.@*METHODS@#A computerized search was performed in the databases including China National Knowledge Infrastructure, Wanfang Data, Weipu, PubMed, Embase, and the Cochrane Library to identify randomized controlled trials of the effect of prophylactic use of hydrolyzed protein formula on gastrointestinal diseases and physical growth in preterm infants. RevMan 5.3 software was used to perform a Meta analysis for the included studies.@*RESULTS@#A total of 7 randomized controlled studies were included. The results of Meta analysis showed that compared with the whole protein formula, the prophylactic use of hydrolyzed protein formula could reduce the risk of neonatal necrotizing enterocolitis (RR=0.40, P=0.04) and feeding intolerance (RR=0.40, P=0.005), and had no significant effect on the growth of weight, length and head circumference (P>0.05).@*CONCLUSIONS@#Compared with the whole protein formula, the prophylactic use of hydrolyzed protein formula in preterm infants may reduce the occurrence of necrotizing enterocolitis and feeding intolerance, and can meet the nutrient requirement of physical development. However, the evidence is limited, and the results of this study cannot support the routine prophylactic use of hydrolyzed protein formula in preterm infants.

Risk factors for necrotizing enterocolitis and establishment of prediction model of necrotizing enterocolitis in preterm infants / 中国当代儿科杂志

OBJECTIVES@#To investigate the risk factors for necrotizing enterocolitis (NEC) in preterm infants, and to establish a scoring model that can predict the development and guide the prevention of NEC.@*METHODS@#A retrospective analysis was performed on the medical data of preterm infants who were admitted to the Department of Neonatology,Bethune First Hospital of Jilin University, from January 2011 to December 2020. These infants were divided into two groups: NEC (298 infants with Bell II stage or above) and non-NEC (300 infants). Univariate and multivariate analyses were performed to identify the factors influencing the development of NEC. A nomogram for predicting the risk of NEC was established based on the factors. The receiver operator characteristic (ROC) curve and the index of concordance (C-index) were used to evaluate the predictive performance of the nomogram.@*RESULTS@#The multivariate logistic regression analysis showed that grade ≥2 intracranial hemorrhage, peripherally inserted central catheterization, breast milk fortifier, transfusion of red cell suspension, hematocrit >49.65%, mean corpuscular volume >114.35 fL, and mean platelet volume >10.95 fL were independent risk factors for NEC (P<0.05), while the use of pulmonary surfactant, the use of probiotics, and the platelet distribution width >11.8 fL were protective factors against NEC (P<0.05). The nomogram showed good accuracy in predicting the risk of NEC, with a bootstrap-corrected C-index of 0.844. The nomogram had an optimal cutoff value of 171.02 in predicting the presence or absence of NEC, with a sensitivity of 74.7% and a specificity of 80.5%.@*CONCLUSIONS@#The prediction nomogram for the risk of NEC has a certain clinical value in early prediction, targeted prevention, and early intervention of NEC.

Uso de probióticos en la prevención de enterocolitis necrotizante / Use of probiotics in the prevention of necrotizing enterocolitis

INTRODUCCIÓN: La enterocolitis necrotizante (ECN) es una patología inflamatoria del sistema digestivo, potencialmente mortal, que afecta a los recién nacidos. Ocurre con mayor frecuencia en recién nacidos prematuros y en especial en aquellos con muy bajo peso de nacimiento (RNMBPN) y extremo bajo peso de nacimiento (RNEBPN). Su fisiopatología es multifactorial, sin embargo, se postula disbiosis intestinal es un factor patogénico importante en su desarrollo. Por consiguiente, se ha propuesto que la administración de probióticos podría tener un rol en la prevención de la ECN en pacientes con alto riesgo. OBJETIVO: Realizar una búsqueda bibliográfica con el objetivo de conocer la evidencia existente en relación al efecto de los probióticos en recién nacidos. RESULTADOS: Los resultados de las revisiones sistemáticas y metanálisis revisados indican que la administración de probióticos reduce el riesgo de ECN, muerte y sepsis tardía en los RNMBPN, no obstante, en el grupo de RNEBPN aun hacen falta estudios. Los estudios que comparan diferentes estrategias de administración de probióticos señalan que los esquemas que incluyen la administración de una mezcla de 2 o más probióticos obtienen los mejores resultados en la prevención de ECN y muerte. Adicionalmente, algunos artículos sugieren un mejor efecto si los esquemas probióticos a utilizar, incluyen especies de los géneros Bifidobacterium y Lactobacillus. CONCLUSIÓN: Existe evidencia en la literatura especializada que apoya el uso de los probióticos en la prevención de ECN y otros desenlaces adversos en los recién nacido prematuros.

Necrotizing enterocolitis (NEC) is a life-threatening inflammatory disease of the digestive system that affects newborns. It occurs most frequently in preterm infants and especially in very low birth weight (VLBW) and extremely low birth weight (ELBW) infants. Its pathophysiology is multifactorial; however, intestinal dysbiosis is postulated to be an important pathogenic factor in its development. Therefore, it has been proposed that the administration of probiotics may have a role in the prevention of NEC in high-risk patients. This update presents a brief overview of the evidence regarding the effect of probiotics in neonates. The results of the systematic reviews and meta-analyses reviewed indicate that probiotic administration reduces the risk of NEC, death and late sepsis in VLBW infants, however, studies are still lacking in the ELBW group. Studies comparing different probiotic administration strategies indicate that schemes that include the administration of a mixture of 2 or more probiotics obtain the best results in the prevention of NEC and death. Additionally, there is some evidence to favor schemes that include species of the genera Bifidobacterium and Lactobacillus. CONCLUSION: There is evidence in the specialized literature that supports probiotic administration may reduces the risk of NEC and other adverse outcomes in preterm infants.

Intervención con probióticos para la prevención de enterocolitis necrotizante en prematuros extremos menores de 1500 gramos o de 32 semanas / Probiotic intervention to prevent necrotizing enterocolitis in extremely preterm infants born before 32 weeks of gestation or with a birth weight of less than 1500 g

Introducción. Existe evidencia del beneficio de los probióticos en prevenir enterocolitis necrotizante en prematuros extremos. Desde 2015, se usa probiótico preventivo en el Servicio de Neonatología, Hospital Hernán Henríquez Aravena, Temuco, Chile.Objetivo. Evaluar el impacto de este probiótico en la incidencia, gravedad, necesidad de terapia quirúrgica y letalidad por enterocolitis necrotizante en prematuros extremos. Pacientes y método. Estudio retrospectivo de cohortes. Datos analizados con Stata. Se aplicó la prueba exacta de Fisher para comparar porcentajes y, para los promedios, la prueba t para varianzas distintas. Los egresados entre 2015 y 2017 recibieron Lactobacillus reuteri Protectis (LRP), dosis única (1 x 108 unidades formadora de colonias) desde los primeros días de vida hasta cumplir las 36 semanas de edad gestacional corregida. Los controles egresados entre 2012 y 2014 no recibieron LRP.Resultados. El 3,45 % de los casos tuvo algún grado de enterocolitis: grado i (el 64 %), ii (el 18 %), iii (el 18 %); requirió cirugía el 18 % y no hubo letalidad. El 3,75 % de los controles históricos presentaron enterocolitis: grado i (el 12 %), ii (el 35 %), iii (el 53 %); el 64,7 % requirió cirugía, y el 47 % falleció. El grupo intervenido presentó grado ii o iii en un 36 %; en el grupo control, la sumatoria de estos estadios fue del 88 %.Conclusión.LRP administrado en dosis única diaria al prematuro extremo no modificó la incidencia de enterocolitis, pero disminuyó su gravedad, la letalidad y necesidad de tratamiento quirúrgico.

Introduction. There is evidence of the beneficial effects of probiotics to prevent necrotizing enterocolitis in extremely preterm infants. Probiotic prevention has been used since 2015 in the Division of Neonatology of Hospital Hernán Henríquez Aravena, Temuco, Chile.Objective. To assess the impact of this probiotic on the incidence, severity, surgical treatment requirement, and fatality rate of necrotizing enterocolitis in extremely preterm infants.Patients and methods. Retrospective, cohort study. Data were analyzed using Stata. Fisher's exact test was used to compare percentages, and the unequal variances t-test, for averages. Infants discharged between 2015 and 2017 received Lactobacillus reuteri Protectis (LRP), in a single dose (1 x 108 colony forming units), since the first days of life until 36 weeks of corrected gestational age. Controls discharged between 2012 and 2014 did not receive LRP.Results. Some degree of enterocolitis was observed in 3.45 % of cases: stage I (64 %), stage II (18 %), stage III (18 %); 18 % required surgery, and there were no deaths. Among historical controls, 3.75 % had enterocolitis: stage I (12 %), stage II (35 %), stage III (53 %); 64.7 % required surgery, and 47 % died. In the intervention group, stage II or III accounted for 36 % of cases, whereas in the control group, for 88 %.Conclusion. Administering a single daily dose of LRP to extremely preterm infants did not affect the incidence of enterocolitis, but reduced its severity, fatality rate, and surgical treatment requiremen

Percepción del equipo de salud sobre los beneficios del calostro como factor protector de enterocolitis necrotizante en recién nacidos prematuros / Health professionals perception about the use of human colostrum, as preventive measure for necrotizing enterocolitis in preterm newborns

INTRODUCCIÓN: La incidencia de enterocolitis necrotizante (ECN), en Chile es de 0,3 a 2,4 por mil recién nacidos vi vos, siendo principalmente afectados los neonatos prematuros, y de 8 a 12 por ciento en prematuros menores a 1.500 gramos. OBJETIVO: Describir la percepción de profesionales de salud sobre el uso de calostro en recién nacidos prematuros, como factor protector de enterocolitis necrotizante. SUJETOS Y MÉTODO: Estudio cualitativo, mediante entrevista semiestructurada a 18 profesionales de la salud en tres hospitales públicos de la región de Valparaíso. La pauta de entrevista incluyó 3 temas: Conocimientos, percepción del suministro temprano de calostro y opinión acerca de la extensión de la medida, y 6 subtemas, 2 para cada tema respectivamente: Autopercepción del nivel de conocimiento y fuentes de información; Experiencia: aspectos positivos/eventos adversos y opinión del calostro como factor protector de enterocolitis; aspectos facilitadores u obstaculizadores y opinión acerca de la medida como política nacional. Procesamiento de datos mediante análisis de contenido cualitativo, temático. RESULTADOS: El uso de calostro en prematuros se da de modo protocolizado en dos de las tres unidades de alta complejidad neonatal de la región de Valparaíso. Los participantes opinan positivamente acerca de los resultados preventivos de esta medida. Aun cuando en un tercer estable cimiento no se aplique, hay una percepción favorable acerca de su potencial beneficio y su bajo costo de implementación. Se señala, no obstante, que ésta requiere de mayor evidencia y de un protocolo de aplicación. Otras limitantes serían la insuficiente dotación y formación del personal, y la necesidad de adquirir equipamiento e insumos. CONCLUSIONES: Profesionales que han aplicado un protocolo de administración de calostro en neonatos prematuros en la Región de Valparaíso, reportan buenos resultados de salud, y promueven la motivación del equipo hacia esta praxis. Sin embargo, se considera relevante la difusión y discusión de protocolos nacionales e internacionales, así como el desarrollo de investigación local. Dadas las experiencias en curso en Chile, y el debate internacional, se considera oportuno que el tema sea abordado y discutido en la comunidad sanitaria nacional.

INTRODUCTION: In Chile, necrotizing enterocolitis (NEC) mainly affects preterm infants, with an incidence of 0.3 to 2.4 per 1,000 live births, and 8 to 12% in preterm infants weighing less than 1,500 grams. OBJECTIVE: To describe health professionals perceptions on the use of human colostrum as a preventive measu re against necrotizing enterocolitis in preterm newborns. SUBJECTS AND METHOD: Qualitative study, using 18 semi-structured individual interviews of health professionals in three public hospitals of the Valparaíso Region. The interview included 3 topics: Knowledge, Perception of early colostrum supply and Opinion about the extent of the measure, and 6 subtopics, 2 for each topic respectively: Self-perception of knowledge level and Sources of information; Experience: positive aspects/adverse events and Opinion of colostrum as a protective factor for enterocolitis; Facilitating or hindering aspects and Opinion about the measure as national policy. Data were processed through qualitative content analysis. RESULTS: Two of the three high-complexity neonatal units of the Valparaíso Re gion have a protocol for administrating colostrum in premature infants. Participants have a positive opinion about the preventive results of this measure. Even in the third hospital where there is no protocol, they have a favorable perception of its potential benefit and its low cost of implementa tion. However, we observed that this procedure requires more evidence and an application protocol. Other limitations would be the lack of staffing and training and the need for equipment and supplies. CONCLUSIONS: Professionals who have applied a colostrum administration protocol in preterm infants in the Valparaíso Region report good health outcomes and promote team motivation towards this practice. However, it is relevant to the dissemination and discussion of national and international protocols, as well as the development of local research. Given the ongoing experiences in Chile and the international debate, we considered appropriate to address and discuss the topic within the na tional health community.

Respuesta de las citocinas a la combinación de simbióticos y lactoferrina en recién nacidos de muy bajo peso al nacer: ensayo controlado aleatorizado / Cytokine responses to symbiotic and lactoferrin combination in very low birth weight neonates: a randomized control trial

Introducción. Los probióticos y prebióticos presentan beneficios potenciales en la inflamacióncrónica de las mucosas, incluida la prevención de la enterocolitis necrosante. No obstante, los mecanismos y resultados de estos efectos inmunomoduladores son confusos. El objetivo fue investigar la respuesta de las citocinas a Lactobacillus y Bifidobacterium asociados con fructo- y galactooligosacáridos (simbióticos) y lactoferrina en recién nacidos de muy bajo peso al nacer.Población y métodos. Se asignó aleatoriamente a lactantes con ≤32 semanas de gestación y ≤1500 g de peso para recibir simbióticos o 1 ml de agua destilada como placebo desde la primera alimentación hasta el alta. Se obtuvieron muestras de sangre los días posnatales 0 ± 2, 14 ± 2 y 28 ± 2, y se midieron interferón-γ, interleucina (IL)-5, IL-10 e IL-17A.Resultados. En el grupo del estudio (n = 25), la concentración de IL-10 disminuyó a lo largo del estudio (p = 0,011), pero no cambió en el grupo de referencia. La concentración de IL-5 se mantuvo constante los primeros 14 días y luego disminuyó significativamente (p= 0,042) en el grupo del estudio, mientras que aumentó en los primeros 14 días (p = 0,019) y luego disminuyó en 28 días (p = 0,011) en el grupo de referencia (n = 25).La concentración de otras citocinas no cambió a lo largo del estudio.Conclusión. El uso combinado de probióticos con oligosacáridos y lactoferrina estuvo asociado con una disminución en la concentración de IL-10, pero no se observó un cambio en las otras citocinas.

Introduction. Probiotics and prebiotics, which are multifunctional agents, have potential benefits in chronic mucosal inflammation, including the prevention of necrotizing enterocolitis. However, the mechanisms and the results of these immunomodulatory effects are not clear. This study aimed to investigate the cytokine response to the combination of Lactobacillus and Bifidobacterium together with fructo- and galacto-oligosaccharides (symbiotic) and lactoferrin in very low birth weight neonates.Population and Methods. Infants ≤ 32 GWs and ≤ 1,500 g were randomly assigned to receive a symbiotic combination or 1 ml distilled water as placebo starting with the first feed until discharge. Blood samples were obtained at postnatal 0 ± 2, 14 ± 2, and 28 ± 2 days, and the serum levels of interferon-γ, interleukin (IL)-5, IL-10, and IL-17A were measured.Results. In the study group (n = 25), the IL-10 levels decreased throughout the study period (p = 0.011) but did not change in the control group. The IL-5 levels remained steady in the first 14 days and decreased significantly thereafter (p = 0.042) in the study group, whereas they increased in the first 14 days (p = 0.019), and then decreased in 28 days (p = 0.011) in the control group (n = 25). The levels of the other cytokines did not change throughout the study period.Conclusion.The combined use of probiotics with oligosaccharides and lactoferrin was associated with a decrease in IL-10 levels, but no change was observed in the other cytokines.

Histological analysis of the intestinal wall of newborn rats submitted to hypoxia and reoxygenation to evaluate the protective effect of N-Acetylcysteine

Abstract Purpose To evaluate the effect of N-Acetylcysteine (NAC) in newborn rats submitted to hypoxia and reoxygenation (H/R) conditions in an experimental model of necrotizing enterocolitis. Methods Eight pregnant rats and their 70 cubs were used (5 groups) and exposed to H/R conditions and received NAC at different times. The animals in the H/R groups were placed in a gas chamber (100% CO2) for 10 minutes and then reoxygenated for 10 minutes (100% O2), twice a day for the first three days of life, with a six-hour span between events. On the third day of life, the animals were anesthetized, laparotomized and the intestines were resected. Results The H/R and NAC groups showed changes in the intestinal wall in relation to the number, height and width of the villi when compared to the control group (p<0.0001), but with better preservation of structures in the NAC group. There were no differences between groups regarding the number (%) of mitoses. Conclusion The administration of NAC decreased the lesions in the intestinal wall of rats submitted to H/R, therefore suggesting that this drug can be used to prevent the development of necrotizing enterocolitis in newborns.

Uso de probióticos como profilaxis de enterocolitis necrotizante en neonatos: revisión temática / Use of probiotics as prophylaxis of necrotising enterocolitis in neonates: systematic review

La Enterocolitis Necrotizante (ECN) es una de las patologías más comunes del tracto gastrointestinal del Recién Nacido (RN). La prevalencia mundial de esta patología es de 7% en RN con peso al nacer entre 500 y 1500 gramos, mientras que en Chile la incidencia de 1,8 por cada 1000 RN. Dada la gravedad y mortalidad que puede alcanzar, se han investigado recursos que pudieran ser útiles para prevenir, como lo son el uso de probióticos. Objetivo: Identificar en la literatura actual la utilidad de la administración de probióticos a neonatos de pretérmino en la profilaxis de ECN. Diseño de estudio: Revisión Bibliográfica. Resultados: Sólo un estudio presentó entre sus resultados una relación directa entre el uso de probióticos con una menor incidencia de ECN en estadio II. En los otros, las diferencias no fueron estadísticamente significativas, sin embargo se describieron efectos como un aumento de tolerancia alimentaria. Conclusiones: Los probióticos mejorarían la tolerancia alimentaria. No se encontraron estudios que prueben asociación con la prevención de ECN, se necesitan líneas de investigación que consideren los posibles efectos adversos que tenga el uso de esta terapia profiláctica, tanto en el tipo de probiótico, inicio o duración de uso

Necrotizing enterocolitis (NEC) is one of the most common diseases in preterm infants' gastrointestinal tract. The world prevalence of this condition is 7% in infants with a birth weight between 500 and 1500 g, while in Chile the incidence is about 1.8 per 1000 newborn. The literature describes preventive approaches such as the use of probiotics. Objective: To identify in the literature the probiotic supplementation utility, for preventing Necrotizing Enterocolitis in preterm infants. Study Design: Systematic Review. Results: Only one study presented results from a direct relationship between the use of probiotics with a lower incidence of NEC stage II. In the other, the differences were not statistically significant, but effects such as an improvement on alimentary tolerance were described. Conclusions: Probiotics improved feeding tolerance. No studies proving association between the use of probiotics with the prevention of NEC were found. It must consider future research's lines to possible adverse effects in use of probiotics, the type of probiotic, the initiation or treatment duration

Neonatal necrotizing enterocolitis rat model attenuated by a remote ischemic preconditioning in the pregnant

Abstract Purpose: To evaluate the effect of remote ischemic preconditioning (r-IPC) administered to pregnant rats, in the ileum of newborn rats subjected to hypoxia and reoxygenation. Methods: We used three pregnant rats and their newborn rats distributed in three groups: 1) Control (C) - Newborn rats born from a pregnant rat which did not undergo any intervention; 2) Hypoxia-Reoxygenation (H/R) - Newborn rats born from a pregnant rat which did not undergo any intervention, and were subjected to hypoxia-reoxygenation; 3) Remote Ischemic Preconditioning (r-IPC) - newborn rats born from a pregnant rat which was subjected to remote ischemic preconditioning twenty-four hours before giving birth and the newborn rats were subjected to hypoxia-reoxygenation. Segments of ileum were prepared for histological analysis by HE and immunohistochemistry by the Ki67 to evaluate cell proliferation, crypt depth and villus height and evaluation of apoptosis by cleaved caspase-3. Results: The intensity of the lesions was lower in the r-IPC than in the H/R group, showing significant difference (p<0.01). The r-IPC group showed a higher proliferative activity compared to the H/R group (p<0.01), with deeper crypts (r-IPC > H/R - p < 0.05), and higher villi, showing significant difference (r-IPC > H/R - (p <0.01). The occurrence of apoptosis in the H/R group was lower in comparison to groups C and r-IPC, with significant difference (H/R < r-IPC; p<0.05). Conclusion: The remote ischemic preconditioning applied to the pregnant rat protected the ileum of newborn rats subjected to hypoxia and reoxygenation, with decreased intensity of the lesions in the ileum mucosa and preservation of proliferative activity, keeping the villus height and crypt depth similar to group C.

prophylactic role of probiotics for preterm neonates

Background: Probiotics are live microorganisms which when administered in adequate amounts confer a health benefit on the host. Probiotics have been used for prevention and treatment of various medical conditions in children and adults.

Studies on probiotics in premature infants have focused on normalizing intestinal flora, improvement in feeding intolerance, prevention of necrotizing enterocolitis which is the leading causes of death in the neonatal intensive care unit

Objective of the Study: was to provide an overview of the controversies regarding probiotic use in preterm infants and to shed light on the practical considerations for implementation of probiotic supplementation

Methods: A Systematic search in the scientific database [Medline, Scopus, EMBASE, and Google Scholer] from 1990 to 2016 was conducted for all relevant retrospective studies including; retrospective, prospective and randomized controlled trials and cohort studies were analyzed and included based on the preset inclusion and exclusion criteria

Results: The search results yielded 16 studies, 12 of which were RCTs with 2340 premature neonates and 4 meta-analyses with 10227 neonates which showed a significantly decreased incidence of Necrotizing Enterocolitis [NEC] [risk ratio, RR = 0.35, 95% confidence interval, 95% CI, 0.23- 0.54; p = 0.0006] and mortality [RR = 0.46, 95% CI, 0.32-0.67; p < 0.0001]

Sepsis did not differ significantly between the two groups [RR = 0.93, 95% CI, 0.76-1.15; p = 0.05]

Conclusion: there is a strong body of evidence supporting that Probiotic supplementation reduces the risk of NEC and mortality in preterm infants yet there is no sufficient evidence to support the optimal strain, dose and timing need further investigation

Inocuidad, prevención y riesgos de los probióticos / Probiotics: innocuousness, prevention and risks

Los probióticos son microorganismos vivos que cuando son administrados en cantidades adecuadas confieren beneficios a la salud del huésped. Su empleo es muy amplio en todas las edades, y los episodios adversos asociados con ellos, incluyendo casos de sepsis, que hagan suponer un riesgo real y manifiesto de invasión del torrente sanguíneo o algún tipo de contagio son muy infrecuentes. Sin embargo, algunos profesionales de la salud manifiestan dudas respecto de su inocuidad. Esta revisión revela que la incidencia de sepsis por probióticos, principalmente lactobacilos y bifidobacterias, evaluada en casuísticas numerosas a lo largo de decenios usando métodos de biología molecular o cultivos, es muy baja: del orden de 0,021% en algunas estadísticas y podría llegar hasta 1 caso/1.000.000 de habitantes. Estos datos son importantes teniendo en cuenta el empleo masivo de diversas especies y cepas, sin restricciones de ninguna especie y en todas las edades. Algunos estudios que comunican otros efectos adversos tienen problemas de diseño que ponen en duda su validez. Por el contrario, se ha demostrado que los probióticos ejercen efectos positivos estimulando la inmunidad innata y adquirida, en el tratamiento de la atopia y eccema y en la prevención de la enterocolitis necrosante en sujetos tan vulnerables como los prematuros.

Probiotics have been defined as live microorganisms which, when ingested in adequate numbers, confer health benefits to the host. They are currently consumed without any age restrictions and adverse effects such as sepsis, a marker of the risk of invasion of the bloodstream, are extremely infrequent. However, some health professionals express doubts about probiotics being truly innocuous. This review discusses the incidence of sepsis secondary to probiotics use, mainly lactobacilli and bifidobacteria, evaluated through molecular biology or classic culture techniques, showing that sepsis in large numbers of individuals along decennia is extremely low, of the order of 0,02% en some centers or as low as 1 case/million population in France. These data are important considering the use different species and strains of these microorganisms. Few studies which have reported other adverse effects but many of these have problems with their design that cast doubt about the validity of their results. On the contrary, it has been shown that probiotic microorganisms exert positive stimulatory effects on innate and acquired immunity, with decrease of the manifestations of atopy and eczema. These positive effects are further evidenced by the beneficial effects of many species of probiotics in preventing necrotizing enterocolitis in patients as functionally labile as premature-born babies.

Ibuprofen and indomethacin for the closure of the patent ductus arteriosus / Ibuprofen, indometacina e fechamento do canal arterial

The ductus arteriosus connects the pulmonary artery with the aorta and allows right ventricular blood to bypass the unexpanded lungs. In mature infants, the ductus arteriosus closes after birth. Patent ductus arteriosus occurs in 70% of preterm infants with a birth weight < 1,000 grams. Failure of the ductus arteriosus to close has been associated with intraventricular hemorrhage, necrotizing enterocolitis, bronchopulmonary dysplasia, periventricular leukomalacia, renal failure, and persistent pulmonary hypertension. The drugs used to treat the patent ductus arteriosus are ibuprofen and indomethacin which are potent non-selective inhibitors of cyclo-oxygenase (COX) and therefore inhibit prostaglandin E2 synthesis. Prostaglandin E2 relaxes smooth muscle and tends to inhibit the closure of the patent ductus arteriosus. Intravenous ibuprofen and indomethacin inhibit prostaglandin E2 synthesis and thereby close the patent ductus arteriosus with similar efficacy. Indomethacin reduces the blood flow velocity in kidneys, intestine and brain. Ibuprofen has less effect on blood flow velocity in these organs. There is a significant increase in serum creatinine after indomethacin administration but not after ibuprofen and infants treated with ibuprofen have higher creatinine clearance. Oliguria (urine output < 1 ml/kg/h) occurs more frequently with indomethacin than with ibuprofen. Indomethacin requires furosemide for urine output more often than ibuprofen. Ibuprofen reduces the risk of necrotizing enterocolitis and transient renal insufficiency and it is the drug of choice for closing the patent ductus arteriosus. Ibuprofen and indomethacin may be administered orally. In conclusion, intravenous ibuprofen and indomethacin close the patent ductus arteriosus at the same rate, but indomethacin is more toxic than ibuprofen.

O canal arterial conecta a artéria pulmonar com a aorta e permite que o sangue oriundo do ventrículo direito evite passar pelos pulmões fetais não expandidos. Em recém-nascidos maduros, o canal arterial se fecha após o nascimento. A persistência do canal arterial ocorre em 70% dos recém-nascidos prematuros com peso de nascimento < 1.000 gramas. O não fechamento do canal arterial associa-se a hemorragia intraventricular, enterocolite necrosante, displasia bronco-pulmonar, leucomalacia periventricular, insuficiência renal e hipertensão pulmonar persistente. Os medicamentos utilizados para tratar a persistência do canal arterial são o ibuprofeno e a indometacina. Ambos são potentes inibidores não seletivos da ciclo-oxigenase e inibem a síntese de prostaglandina E2. Esta relaxa a musculature vascular lisa e tende a inibir o fechamento do canal arterial. O ibuprofeno e a indometacina inibem a síntese de prostaglandina E2 e favorecem o fechamento do canal arterial. A indometacina reduz a velocidade do fluxo sanguíneo renal, intestinal e cerebral. O Ibuprofeno tem efeito menor sobre a velocidade do fluxo de sangue nesses órgãos. Há um aumento significativo da creatinina sérica após a administração de indometacina, mas não após o ibuprofeno; por isso, recém-nascidos tratados com ibuprofeno têm maior depuração da creatinina. A oligúria ocorre mais frequentemente com a indometacina vs. ibuprofeno. A indometacina requer furosemida para a produção de urina mais frequentemente do que o ibuprofeno. O ibuprofeno reduz o risco de enterocolite necrotizante e de insuficiência renal transitória e é a droga de escolha para o fechamento do canal arterial patente. O ibuprofeno e a indometacina podem ser ministrados por via oral. Em conclusão, o ibuprofeno e a indometacina fecham o canal arterial patente com a mesma velocidade, mas a indometacina é mais tóxica.

A double-blinded randomized trial on growth and feeding tolerance with Saccharomyces boulardii CNCM I-745 in formula-fed preterm infants / Ensaio duplo-cego randomizado sobre crescimento e tolerância de alimentação com a Saccharomyces boulardii CNCM I-745 em neonatos prematuros alimentados com fórmula

Abstract Objective: The use of probiotics is increasingly popular in preterm neonates, as they may prevent necrotizing enterocolitis sepsis and improve growth and feeding tolerance. There is only limited literature on Saccharomyces boulardii CNCM I-745 (S. boulardii) in preterm infants. Method: A prospective, randomized, case-controlled trial with the probiotic S. boulardii (50 mg/kg twice daily) was conducted in newborns with a gestational age of 30-37 weeks and a birth weight between 1500 and 2500 g. Results: 125 neonates were enrolled; 63 in the treatment and 62 in the control group. Weight gain (16.14 ± 1.96 vs. 10.73 ± 1.77 g/kg/day, p < 0.05) and formula intake at maximal enteral feeding (128.4 ± 6.7 vs. 112.3 ± 7.2 mL/kg/day, p < 0.05) were significantly higher in the intervention group. Once enteral feeding was started, the time needed to reach full enteral feeding was significantly shorter in the probiotic group (0.4 ± 0.1 vs. 1.7 ± 0.5 days, p < 0.05). There was no significant difference in sepsis. Necrotizing enterocolitis did not occur. No adverse effects related to S. boulardii were observed. Conclusion: Prophylactic supplementation of S. boulardii at a dose of 50 mg/kg twice a day improved weight gain, improved feeding tolerance, and had no adverse effects in preterm infants >30 weeks old.

Resumo Objetivo: O uso de probióticos está cada vez mais popular em neonatos prematuros, já que podem prevenir a enterocolite necrosante (ECN) e a sepse e aumentar o crescimento e a tolerância de alimentação. Há apenas uma literatura limitada sobre a Saccharomyces boulardii CNCM I-745 (S. boulardii) em neonatos prematuros. Método: Um ensaio de caso-controle prospectivo randomizado com o probiótico S. boulardii (50 mg/kg duas vezes por dia) foi feito com recém-nascidos com idade gestacional de 30 a 37 semanas e peso ao nascer entre 1.500 e 2.500 g. Resultados: Foram incluídos 125 neonatos, 63 no grupo de tratamento e 62 no de controle. O ganho de peso (16,14 ± 1,96 em comparação com 10,73 ± 1,77 g/kg/dia, p < 0,05) e a ingestão de fórmula com nutrição enteral máxima (128,4 ± 6,7 em comparação com 112,3 ± 7,2 mL/kg/dia, p < 0,05) foram significativamente maiores no grupo de intervenção. Assim que a nutrição enteral foi iniciada, o tempo necessário para atingir a nutrição enteral completa foi significativamente menor no grupo probiótico (0,4 ± 0,1 em comparação com 1,7 ± 0,5 dia, p < 0,05). Não houve diferença significativa em sepse. Não ocorreu ECN. Não foi observado efeito colateral relacionado à S. boulardii. Conclusão: A suplementação profilática de S. boulardii em uma dose de 50 mg/kg duas vezes por dia melhorou o ganho de peso, aumentou a tolerância de alimentação e não teve efeito colateral em neonatos prematuros > 30 semanas de idade.

Accuracy of Percutaneous Core Biopsy in the Diagnosis of Small Renal Masses (≤4.0 cm): A Meta-analysis

Objective To use meta-analysis to determine the accuracy of percutaneous core needle biopsy in the diagnosis of small renal masses (SMRs≤4.0 cm). Materials and Methods Studies were identified by searching PubMed, Embase, and the Cochrane Library database up to March 2013. Two of the authors independently assessed the study quality using QUADAS-2 tool and extracted data that met the inclusion criteria. The sensitivity, specificity, likelihood ratios, diagnostic odds ratio (DOR) and also summary receiver operating characteristic (SROC) curve were investigated and draw. Deek’s funnel plot was used to evaluate the publication bias. Result A total of 9 studies with 788 patients (803 biopsies) were included. Failed biopsies without repeated or aborted from follow-up/surgery result were excluded (232 patients and 353 biopsies). For all cases, the pooled sensitivity was 94.0% (95% CI: 91.0%, 95.0%), the pooled positive likelihood was 22.57 (95% CI: 9.20-55.34), the pooled negative likelihood was 0.09 (95% CI: 0.06-0.13), the pooled DOR was 296.52(95% CI: 99. 42-884.38). The area under the curve of SROC analysis was 0.959±0.0254. Conclusion Imaging-guided percutaneous core needle biopsy of small renal masses (SMRs≤4.0 cm) is highly accurate to malignant tumor diagnosis with unknown metastatic status and could be offered to some patients after clinic judgment prior to surgical intervention consideration. .

A meta-analysis of probiotics for preventing necrotizing enterocolitis in preterm neonates

Necrotizing enterocolitis (NEC) is one of the most common acquired diseases of the gastrointestinal tract in preterm infants. Some randomized, controlled trials (RCTs) have indicated that probiotics may potentially lower the incidence of NEC and mortality. However, debate still remains about the safety of probiotics and their influence on normal infant growth. We performed this meta-analysis to assess the safety and benefits of probiotic supplementation in preterm infants. We searched in PubMed, Embase, and Cochrane databases for English references, and in Wanfang, VIP, and CNKI databases for Chinese references. Ultimately, 27 RCTs (including 9 Chinese articles) were incorporated into this meta-analysis. Relative risk (RR) and weighted mean difference (WMD) were calculated using a random-effects or fixed-effects model, depending on the data type and heterogeneity. A total of 6655 preterm infants, including the probiotic group (n=3298) and the placebo group (n=3357), were eligible for inclusion in this meta-analysis. For Bell stage ≥I and gestational age <37 weeks, risk of NEC incidence was significantly lower in the probiotic group [RR=0.35, 95% confidence interval (CI)=0.27-0.44, P<0.00001]. For Bell stage ≥II or gestational age <34 weeks, there were likewise significant differences between the probiotic and placebo groups concerning NEC incidence (RR=0.34, 95%CI=0.25-0.48, P<0.00001; and RR=0.39, 95%CI=0.27-0.56, P<0.00001). Risk of death was significantly reduced in the probiotic group (RR=0.58, 95%CI=0.46-0.75, P<0.0001). In contrast, there was no significant difference concerning the risk of sepsis (RR=0.94, 95%CI=0.83-1.06, P=0.31). With respect to weight gain and the age at which infants reached full feeds, no significant differences were found between the probiotic and placebo groups (WMD=1.07, 95%CI=−0.21-2.34, P=0.10; and WMD=−1.66, 95%CI=−3.6-0.27, P=0.09). This meta-analysis has shown that, regardless of gestational age and NEC stage, probiotic supplementation could significantly reduce the risk of NEC in preterm infants. Analysis also indicated that such supplementation did not increase the incidence risk of sepsis or of mortality. Finally, the study showed that probiotic supplementation may have no adverse effect on normal feeding and growth.

Nutrição precoce de neonatos prematuros estáveis e pequenos para a idade gestacional: um ensaio clínico randomizado / Very early feeding in stable small for gestational age preterm infants: a randomized clinical trial

OBJETIVO: Examinar o efeito da nutrição precoce sobre o tempo para atingir a nutrição completa em neonatos prematuros (PIG) estáveis pequenos para a idade gestacional. MÉTODO: Os neonatos prematuros com idade gestacional inferior a 37 semanas e peso ao nascer inferior a 10% foram alocados aleatoriamente para um regime de nutrição precoce (nas primeiras 24 horas de vida) ou tardia (após as primeiras 24 horas de vida). Todos os neonatos apresentaram uma evidência intrauterina de fluxo diastólico reverso ou ausente. Os neonatos incapazes de iniciar uma nutrição precoce foram excluídos. O tempo para a alimentação completa, a progressão da nutrição e morbidez correspondente foram comparados. A eletrogastrografia (EGG) foi utilizada para mensurar a motilidade gástrica pré e pós-prandial no segundo e no sétimo dias após o início da nutrição. RESULTADOS: Foram incluídos 60 neonatos no estudo, sendo 30 em cada grupo. Os neonatos incluídos no regime de nutrição precoce atingiram a nutrição enteral completa antes dos neonatos do grupo de controle (98±80-157 em comparação a 172±1 23-261 horas de idade, respectivamente; p = 0,004) e recebiam alta hospitalar antes (p = 0,04). Nenhuma enterocolite necrosante (ECN) foi comprovada em ambos os grupos de estudo. A motilidade gástrica melhorou no sétimo dia após o início da nutrição em ambos os grupos de estudo, sem diferença entre eles. CONCLUSÕES: Os neonatos prematuros PIG estáveis em regime de nutrição precoce atingiram alimentação enteral completa e receberam alta hospitalar significativamente antes que aqueles em regime de nutrição tardio, sem morbidez excedente.

OBJECTIVE: To examine the effect of initiating very early feeding on time-to-reach full feeding in stable, small for gestational age (SGA) preterm infants. METHOD: Preterm infants with gestational age below 37 weeks and birth weight below the 10th percentile were randomly allocated to a very early (within 24 hours of birth) feeding regimen or delayed (after 24 hours of birth) feeding. All infants had in utero evidence of absent or reverse diastolic flow. Infants unable to start early feeding were excluded. Time-to-reach full feeding, feeding progression, and related morbidity were compared. Electrogastrography (EGG) was used to measure pre- and postprandial gastric motility on the second and seventh day after feeding initiation. RESULTS: Sixty infants were included in the study, 30 in each group. Infants included in the very early feeding regimen achieved full enteral feeding sooner than controls (98±80-157 vs. 172±123-261 hours of age, respectively; p = 0.004) and were discharged home earlier (p = 0.04). No necrotizing enterocolitis (NEC) was documented in both study groups. Gastric motility was improved at day seven after feeding initiation in both study groups, with no difference between groups. CONCLUSIONS: Stable SGA preterm infants on a very early feeding regimen achieved full enteral feeding and were discharged home significantly earlier than those on a delayed regimen, with no excess morbidity.

Estudio prospectivo y randomizado de suplementación de hierro temprana versus tardía en niños con peso al nacer menor de 1.301 g / Prospective randomized study of early versus late enteral iron supplementation in children who weighed < 1, 301 grams at birth

Objetivo: Determinar si la suplementación temprana de hierro disminuye la necesidad, el número y volúmen de glóbulos rojos transfundidos, en relación a la suplementación tardía de hierro en niños con peso de nacimiento menor a 1.301 g. Pacientes y Método: Recién nacidos de muy bajo peso (RNMPN) fueron randomi-zados a recibir suplementación temprana de hierro de 3 mg/kg/día, tan pronto estaban tolerando alimentación enteral de 100 ml/kg/día, o a los 61 días de vida como suplementación tardía. Se midió niveles de hemoglobina al inicio de la suplementación temprana de hierro y a los 2 meses de vida. La transfusión de glóbulos rojos fue restringida de acuerdo a las guías de transfusión y no se administró eritropoyetina. Resultados: No hay diferencias en el número de transfusiones de glóbulos rojos entre los grupos y en relación a las morbilidades asociadas con la prematuridad no habría diferencias significativas. Conclusiones: La suplementación temprana de hierro cuando el niño este tolerando 100 ml/kg/día de leche, no disminuiría la incidencia de las transfusiones de glóbulos rojos en relación al inicio tardío de hierro a los 61 días de vida y probablemente sea segura en los niños menores de 1.301 g.

Objective: Determine whether early iron supplementation would decrease the need, the number and volume of transfused red blood cells in relation to late iron supplementation in children with birth weight less than 1,301 g. Patients and Methods: Very low birth weight (VLBW) infants were randomly assigned to receive early iron supplementation of 3 mg/kg/day as soon as they could tolerate enteral feeding of 100 ml/kg/day, or at 61 days of life as late supplementation. Hemoglobin levels were measured at the beginning of early iron supplementation and at 2 months of age. The red blood cell transfusion was performed according to transfusion guidelines and erythropoietin was not administered. Results: No differences were observed regarding the number of red cell transfusions between the groups. Morbidities associated with prematurity presented no significant differences. Conclusions: Early iron supplementation to a child that is tolerating 100 mL/kg/day of milk, does not decrease the incidence of red blood cell transfusions compared to late start iron at 61 days of life, and it is probably safe in infants with birth weight < 1,301 g.

Eficácia dos probióticos na profilaxia de enterocolite necrosante em recém-nascidos prematuros: revisão sistemática e meta-análise / Effectiveness of probiotics in the prophylaxis of necrotizing enterocolitis in preterm neonates: a systematic review and meta-analysis

OBJETIVO: Elucidar os benefícios do uso de probióticos na prevenção de enterocolite necrosante (ECN) e de suas complicações em recém-nascidos prematuros. MÉTODO: Revisão sistemática de ensaios clínicos randomizados, que incluiu pesquisas efetuadas em três bases de dados (MEDLINE, EMBASE e LILACS), utilizando a combinação dos termos (necrotizing enterocolitis) AND (probiotics). RESULTADOS : Foram incluídos 11 ensaios clínicos randomizados, totalizando 2.887 pacientes, sendo 1.431 no grupo Probiótico e 1.456 no grupo Controle. Houve redução na incidência de ECN (NNT = 25), de morte global (NNT = 34) e sepse neonatal (NNT = 34) no grupo Probiótico em relação ao grupo Controle. Pacientes alimentados com suplementação de probióticos tiveram tempo de reintrodução alimentar (p < 0,001) e de hospitalização (p < 0,001) menor quando comparados aos que não receberam. Não houve diferença na mortalidade causada por ECN. CONCLUSÃO: Em recém-nascidos prematuros, o uso de probióticos é eficaz na profilaxia de ECN e de suas complicações.

OBJECTIVE: To elucidate the benefits of using probiotics in the prevention of necrotizing enterocolitis (NEC) and its complications in preterm newborns. METHOD: This was a systematic review of randomized controlled trials, which included studies retrieved from three databases (MEDLINE, Embase, and LILACS), using a combination of the terms (necrotizing enterocolitis) AND (probiotics). RESULTS: 11 randomized trials were included, totaling 2,887 patients, 1,431 in the probiotic group and 1,456 in the control group. There was a reduction in the incidence of NEC (NNT = 25), overall death (NNT = 34), and neonatal sepsis (NNT = 34) in the probiotic group compared to the control group. Patients that received probiotic supplementation had lower food reintroduction time (p < 0.001) and hospitalization time (p < 0.001) when compared to those not receiving probiotics. There was no difference in mortality caused by NEC. CONCLUSION: In premature newborns, the use of probiotics is effective as a prophylaxis for NEC and its complications.